Process for the preparation n-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methane sulfonamido-dibenzo[b,d]furan-1-carboxamide

A method for the preparation of a compound of formula (E-Ia)

• where
• R is a substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylakyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, or substituted or unsubstituted heterocyclylalkyl, and
• R1 is hydrogen, which comprises the step of reacting 4-hydroxy-8-nitro-1-formyl dibenzofuran (E)
• with an amine of the formula R—NH2, where R is as defined above, to yield a compound of formula (E-Ia).

A method for the preparation of a compound of formula (E-Ic)

• where
• R is substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylakyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, or substituted or unsubstituted heterocyclylalkyl, and
• R1 is a substituted or unsubstituted C1-6 alkyl, which comprises the step of alkylation of a compound of formula (E-Ia)
• where R1 is hydrogen and R is as defined above, to yield a compound of formula (E-Ic).

A method for the synthesis of N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfonamido-dibenzo[b,d]furan-1-carboxamide or a pharmaceutically acceptable salt thereof which comprises the step of converting a compound having the forumua:

• where
• R1 is hydrogen or a substituted or unsubstituted C1-6 alkyl, and
• PG is an aldehyde protecting group;
• to N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfonamido-dibenzo[b,d]furan-1-carboxamide or a pharmaceutically acceptable salt thereof.

A compound selected from:

• 4-cyclopentoxy-3-(4′-nitro-3′bromophenoxy)-benzaldehyde (C);
• 1-{[(4-methylphenyl)imino]methyl }-8-nitro-dibenzo[b,d]furan -4-ol (E1);
• 1-{[(4-methylphenyl)imino]methyl}-4-difluoromethoxy-8-nitro-dibenzo[b,d]furan (E2);
• and
• p-nitrophenyl 4-difluoro methoxy-8-nitro dibenzofuran carboxylic acid ester (H).

N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfonamido-dibenzo[b,d]furan-1-carboxamide or a pharmaceutically acceptable salt thereof containing an amount less than 0.15% of:

• 4-cyclopentoxy-3-(4′-nitro-3′bromophenoxy)-benzaldehyde;
• a compound of the formula
• where
• R1 is hydrogen or a substituted or unsubstituted C1-6 alkyl, and
• PG is an aldehyde protecting group;
• 1-{[(4-methylphenyl)imino]methyl}-8-nitro-dibenzo[b,d]furan-4-ol (E1);
• 1-{[(4-methylphenyl)imino]methyl }-4-difluoromethoxy-8-nitro-dibenzo[b,d]furan (E2);
• or
• p-nitrophenyl 4-difluoro methoxy-8-nitro dibenzofuran carboxylic acid ester (H).